Genetic Association of ACE2 rs2285666 (C>T) and rs2106809 (A>G) and susceptibility to SARS-CoV-2 infection among the Ghanaian population.

Alexander Owusu Boakye^1,2Christian Obirikorang^1,2Anthony Afum-Adjei Awuah^1,2Evans Asamoah Adu^1,2Doris Winter³Eric Ebenezer Boham^1,2Hakim Alani¹Sylvester Kofi Newton¹Nana Safi Toure Almoustapha¹James Deke¹Welbeck Odame Dzadey¹Louis Adu-Amoah^1,2Sally-Ann Kroduah^1,4Mary Ama Grant¹Gracelyn Asare¹Amos Amoako-Adusei¹Wibke Loag³Jenny Kettenbeil⁵Yaw Adu-Sarkodie⁶Ebenezer Oduro-Mensah⁷Alfred Edwin Yawson⁸Stephen Apanga⁹Rose Adjei Odotei^1,4Austin Gideon Adobasom-Anane^1,4Eva Lorenz^10,11,3Aurelia Souares^10,12Oumou Maiga-Ascofare^1,10,5Juergen May^10,13,5Nicole S. Struck^10,3*John Humphery Amuasi^1,13,4,5*

• ¹Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana
• ²Department of Molecular Medicine, School of Medicine and Denistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
• ³Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Hamburg, Germany
• ⁴School of Public Health, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
• ⁵Bernhard Nocht Institute for Tropical Medicine (BNITM), Hamburg, Hamburg, Germany
• ⁶Department of Clinical Microbiology, School of Medicine and Denistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
• ⁷GA East Hospital, Accra, Ghana
• ⁸Medical School, University of Ghana, Accra, Ghana
• ⁹Department of Community Health and Preventive Medicine, School of Medicine, University for Development Studies, Tamale, Ghana
• ¹⁰German Center for Infection Research (DZIF), Partner Site Hamburg Lübeck Borstel Riems, Hamburg, Hamburg, Germany
• ¹¹Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Rhineland-Palatinate, Germany
• ¹²Heidelberg Institute of Global Health, Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany
• ¹³Department of Tropical Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters human cells using the angiotensin-converting enzyme 2 (ACE-2) receptor. ACE2 single nucleotide polymorphisms (SNPs) can influence susceptibility by affecting viral binding or gene expression. This study investigated the association between ACE2 SNPs, rs2285666 and rs2106809, and the SARS-CoV-2 infection susceptibility in a Ghanaian population.Genomic DNA was extracted, using a magnetic bead-based method, from blood samples of a random-subset of 1,334 participants drawn from a two-stage cluster, population-based household cross-sectional SARS-CoV-2 IgG seroprevalence survey. Data collected included, socio-demographic characteristics, medical history, vaccination, and smoking status.Genotyping of the ACE2 SNPs was performed using Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) combined with melting curve analysis. Logistic regression models were utilized to assess the association between the ACE2 SNPs and the susceptibility to SARS-CoV-2 infection.The median age of participants was 33 (Interquartile range [IQR] = 24 -46) years. Females accounted for the majority of the sampled population, 64.3%. SARS-CoV-2-IgG seropositivity was (58.4%, 95%CI: 52.6% -64.2%) among the male population and (54.1%, 95%CI: 49.54% -58.61%) in the female population. There were no significant differences in overall allele or genotype frequencies of ACE2 SNPs between SARS-CoV-2 IgG seropositive and seronegative individuals for both females and males. Among females, those with the T allele of ACE2 rs2285666 had a 38% decreased susceptibility to SARS-CoV-2 infection under the dominant (adjusted odds ratio [aOR] = 0.62; 95%CI = 0.45 -0.85, P= 0.003) and heterozygous advantage models (aOR = 0.62; 95%CI = 0.45 -0.86, P= 0.004), after adjusting for confounders, but not the recessive model (aOR = 0.41; 95%CI = 0.03 -5.22, P= 0.490). No significant association was observed among males. Overall, the ACE2 rs2106809 was not associated with the susceptibility to SARS-CoV-2 infection in both males and females.This study found no for association between ACE2 rs2106809 genetic variant and susceptibility to SARS-CoV-2 infection, whilst the rs2285666 T-allele was associated with a decreased frequency for SARS-CoV-2 infection among Ghanaian females. These findings enhance our understanding of genetic factors influencing SARS-CoV-2 susceptibility, which could help identify at-risk populations and inform more targeted public health interventions in future outbreaks.